Stress Damage Research Articles

The Effectiveness of Steroids and Antioxidants in the Management of Cisplatin-induced Ototoxicity: A Comprehensive Systematic Review of the Literature and Network Meta-Analysis

Abstract Background: Cisplatin efficacy in cancer therapy is hindered by dose-dependent toxicities, including ototoxicity. Its mechanisms involve cochlear damage and oxidative stress. Gender and age affect susceptibility, with limited treatment options for adults. Objective: To assess the effectiveness of steroids compared to antioxidants (AOs) in preventing and managing cisplatin-induced ototoxicity. Materials and Methods: Data were collected from multiple sources including Medline, CENTRAL, PubMed, and Springer Nature Journals. Adults and pediatrics with the clinical diagnosis of cisplatin-induced ototoxicity, interventional studies (including single-arm studies) were included. Studies with a focus on chemotherapy agents other than cisplatin were excluded. Results: The study encompassed 10 randomized controlled trials spanning 2004–2023 across Canada, Israel, The Netherland, Spain, Turkey, Greece, Italy, and Iran. It aimed to evaluate interventions for preventing cisplatin-induced ototoxicity, including intratympanic injections and oral dietary supplements. Based on the results of this systematic review, thiosulfate-hyaluronate gel showed a 1.3 dB reduction in hearing loss; dexamethasone injections had minimal efficacy; L-N-acetylcysteine (L-NAC) offered significant otoprotection with daily infusion; and transtympanic L-NAC showed no significant benefit. Salicylate usage yielded no decrease in hearing loss. AO dietary supplements showed no difference in results between groups. However, based on the network meta-analysis results, it appears that steroids perform best in reducing cisplatin-induced ototoxicity at higher frequencies (8000 Hz), followed by placebo and then AO. Conclusion: A further molecular and targeted therapy is needed to target the cyto/ototoxic activity and further prevent such deterioration in hearing and promote chemotherapy regime without ototoxic effects.

Anti-diabetic effects of marine natural products through redox modulation via Nrf2/HO-1 cytoprotective pathways

Diabetes mellitus (DM), a major global health concern, is a chronic metabolic disorder. Bioactive compounds sourced from numerous marine natural products recently have drawn attention as novel therapeutic approaches. Considering these chemicals and their role in cellular redox modulation by involving the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway, the current study attempts to highlight their anti-diabetic effects and the molecular mechanisms involved. Reactive oxygen species (ROS)-mediated oxidative stress, inflammation, and cellular damage are linked to most human pathologies specifically DM. The Nrf2/HO-1 pathway is a key defense mechanism developed by the cells to combat ROS burst. Marine natural compounds have strong pharmacological potential in triggering cellular antioxidant defense mechanisms by declining oxidative damage and inflammation linked to DM. How marine natural products potentially alleviate DM specifically type 2 diabetes (T2D) and its related issues is especially focused on. The literature was thoroughly analyzed to open a discussion about specific marine compounds and their well-established anti-diabetic effects to elucidate possible therapeutic applications. Furthermore, opportunities and the pros and cons of using these marine bioactive compounds as complementary treatment for DM are also discussed. The diverse characteristics of marine natural products, specifically with regard to redox control, offer promising opportunities for drug discovery and therapeutic interventions in clinical trials.

Progress in the study of toxic effects of drugs on the male reproductive system

This paper provides a comprehensive summary of the toxic effects of drugs on the male reproductive system, with a special focus on the mechanisms of testicular and sperm damage caused by chemotherapeutic agents, antibiotics, and immunosuppressants. Drug-induced reproductive toxicity usually manifests through multiple pathways including direct injury, interference with hormone regulation, oxidative stress, and DNA damage. These mechanisms can lead to impaired spermatogenesis, decreased testicular function, and long-term infertility, thereby seriously affecting male reproductive health. Specifically, chemotherapeutic drugs, such as cisplatin and cyclophosphamide, have been widely documented to cause direct damage to the testes, leading to significant decreases in sperm quantity and quality. Antibiotics and nonsteroidal anti-inflammatory drugs also negatively affect reproductive function by affecting mitochondrial function and inducing oxidative stress in the testicular cells. Although important advances have been made in recent years in the study of drug-induced reproductive toxicity, further exploration is needed to assess the variability of individual responses to drugs and develop long-term protective measures. Future research should focus on developing accurate toxicity assessment methods, customized therapeutic regimens, and enhanced fertility protection strategies, such as the use of antioxidants and methods for the cryopreservation of testes and sperm. Interdisciplinary collaboration will provide new solutions for balancing disease treatment and fertility preservation, especially in the use of high-risk drugs, such as anticancer therapies, where achieving both efficacy and reproductive health will be an important clinical challenge.

Abstract 4137907: Elevated Plasma Neopterin Levels in Patients with Takotsubo Cardiomyopathy

Background: Takotsubo cardiomyopathy (TC) is characterized by left ventricular apical ballooning and intact coronary arteries. The pathogenesis of this disorder is likely to be catecholamine-mediated myocyte damage, microvascular dysfunction and subsequent oxidative stress; however, a number of possible alternative theories have been suggested. Neopterin is produced by activated macrophages following stimulation by interferon-g produced by T-lymphocytes and is capable of enhancing the oxidative potential of reactive oxygen species. The aim of this study was to compare plasma neopterin levels between TC patients and patients with coronary artery disease. Methods: Plasma neopterin levels were measured on admission in patients with TC (n=37), stable angina pectoris (SAP, n=66), unstable angina pectoris (UAP, n=72) and acute myocardial infarction (AMI, n=67) using HPLC. A frozen myocardium specimen was obtained by biopsy from a patient with TC and stained for neopterin, macrophages, and microvessels using immunohistochemistry. Results: Plasma neopterin levels were significantly higher in TC patients compared with SAP patients ( P <0.0001) or UAP patients ( P <0.05), although they were not significantly different from those in AMI patients. In TC patients, plasma neopterin levels correlated positively with neutrophil count (R=0.47, P<0.05) and serum C-reactive protein levels (R=0.38, P<0.05). Immunohistochemical staining showed abundant neopterin-positive macrophages in the myocardium specimen from the patient with TC. Conclusions: This study demonstrates, for the first time, that plasma neopterin levels are elevated in TC patients compared with those in SAP and UAP patients. These findings suggest that neopterin may play an important role in the pathophysiology of Takotsubo cardiomyopathy.

Isofraxidin alleviated radiation-induced testicular damage via the Nrf2/HO-1-NLRP3/ASC Axis

OBJECTIVE: Radiotherapy is used to treat patients with tumors; however, radiation (IR)-induced testicular injury, which has no effective treatment approved in clinical practice, significantly influences their prognosis and quality of life. The protective effects and underlying mechanisms of action of isofraxidin (IF) against IR-induced testicular injury were investigated. Methods: A mouse testis injury model was established using 5 Gy irradiation. H&E staining, immunofluorescence staining, and enzyme-linked immunosorbent assay were used to measure DNA damage, apoptosis, inflammatory reactions, and oxidative stress in the testes of mice after irradiation. The effectiveness of IF irradiation on testicular injury was evaluated, and the mechanisms of the related oxidative stress and inflammatory response pathways are discussed. Results: IF can improve IR-induced testicular injury by inhibiting the increased levels of DNA damage, apoptosis rate, oxidative stress, and inflammatory factors. The radioprotective effects of IF on testicular injury are mediated by the stimulation of Nrf2/HO-1 or suppression of NLRP3 inflammasome signaling pathways. In addition, crosstalk between the Nrf2/HO-1 and NLRP3 inflammasome signaling pathways was elucidated, in which the inhibition of the NLRP3 inflammasome was mediated by the activation of Nrf2 signaling with IF upon IR exposure. Conclusion: IF can be a potent radioprotective agent to mitigate testicular damage, and may provide a new therapeutic option to alleviate the side effects of radiotherapy in male patients with tumors.

Anti-Obesity Effects of Adzuki Bean Saponins in Improving Lipid Metabolism Through Reducing Oxidative Stress and Alleviating Mitochondrial Abnormality by Activating the PI3K/Akt/GSK3β/β-Catenin Signaling Pathway

Obesity is a chronic and complex disease defined by the excessive deposition of fat and is highly associated with oxidative stress. Adzuki bean saponins (ABS) showed anti-obesity activity in our previous in vivo study; however, the active saponins of adzuki beans and potential mechanisms are still unclear. This research aims to elucidate the anti-obesity effects of ABS in improving lipid metabolism and oxidative stress, exploring the effective ingredients and potential molecular mechanisms through UHPLC-QE-MS analysis, network pharmacology, bioinformatics, and in vitro experiments both in the 3T3-L1 cell line and HepG2 cell line. The results indicate that ABS can improve intracellular lipid accumulation, adipogenesis, oxidative stress, and mitochondrial damage caused by lipid accumulation including ROS generation, abnormal mitochondrial membrane potential, and ATP disorder. Fifteen saponin components were identified with the UHPLC-QE-MS analysis. The network pharmacology and bioinformatics analyses indicated that the PI3K/Akt signaling pathway is associated with the bioactive effect of ABS. Through Western blotting and immunofluorescence analysis, the anti-obesity effect of ABS is achieved through regulation of the PI3K/Akt/GSK3β/β-catenin signaling pathway and activation of downstream transcription factor c-Myc in the lipid accumulation cell model, and regulation of β-catenin signaling and inhibition of downstream transcription factor C/EBPα in the adipocyte cell model. These results illustrate the biological activity of ABS in improving fat metabolism and oxidative stress by restoring mitochondrial function through β-catenin signaling, the PI3K/Akt/GSK3β/β-catenin signaling pathway, laying the foundation for its further development.

L-Tryptophan improves the sperm quality of threatened Abant trout (Salmo abanticus) against glyphosate toxicity: impact on oxidative stress and DNA damage

The current study focused on the ameliorating impact of TRP (5 mM) on Salmo abanticus spermatozoa exposed to sub‑lethal concentrations of GLY (2.5, 5, and 10 mg/L). Sperm quality parameters, oxidative stress indices, and DNA damage were analyzed in the post‑exposure sperm. Our data reveal that GLY has an adverse effect on motility rate and duration, sperm kinetics parameters, antioxidant status and DNA damage, and triggers antioxidant defense mechanisms at the highest dose (10 mg/L) and it has insufficient therapeutic effect. Overall, GLY poses potential hazards to male reproductive cells and may adversely affect subsequent generations of natural populations.

CSIG-14. ACROLEIN INDUCES THE MIR-30A-5P/NCAM AXIS THROUGH THE AKT/GSK3Β/Β-CATENIN PATHWAY, PROMOTING GLIOMA PROGRESSION

Abstract Glioblastoma (GBM), the most aggressive brain tumor, exhibits resistance to treatment and thrives in low-oxygen (hypoxic) environments, leading to the accumulation of reactive oxygen species (ROS). Hypoxia activates the hypoxia-inducible factor (HIF)-1α pathway, enhancing tumor malignancy. Acrolein, a reactive aldehyde produced during lipid peroxidation in hypoxia, induces toxicity through DNA damage, inflammation, mitochondrial dysfunction, and oxidative stress. Our previous study found elevated acrolein levels in hypoxic glioma cells and linked acrolein-induced DNA damage (Acr-dG) with poor GBM prognosis. However, the role of acrolein in GBM progression remains unclear. This study aims to elucidate the impact of acrolein on GBM. In vitro experiments demonstrated acrolein production under hypoxia, which increased glioma cell migration and spheroid formation. RNA sequencing identified five affected pathways: cell adhesion molecules, PI3K-AKT signaling, ECM-receptor interaction, MAPK signaling, and neuroactive ligand-receptor interaction. Acrolein downregulated NCAM (neural cell adhesion molecule) via the miR-30a-5p-AKT-GSK3β/β-catenin axis in GBM cell lines and patient-derived cells. Overexpressing NCAM reduced cell migration and spheroid formation. Lower NCAM levels in GBM tissues correlated with poor patient survival. This study suggests the potential of NCAM as a therapeutic target for GBM and provides insights into early detection and treatment strategies for this malignancy.

CSIG-15. ACROLEIN INDUCES THE MIR-30A-5P/NCAM AXIS VIA THE AKT/GSK3Β/Β-CATENIN PATHWAY, PROMOTING GLIOMA PROGRESSION

Abstract Glioblastoma (GBM), the most aggressive brain tumor, exhibits resistance to treatment and thrives in low-oxygen (hypoxic) environments, leading to the accumulation of reactive oxygen species (ROS). Hypoxia activates the hypoxia-inducible factor (HIF)-1α pathway, enhancing tumor malignancy. Acrolein, a reactive aldehyde produced during lipid peroxidation in hypoxia, induces toxicity through DNA damage, inflammation, mitochondrial dysfunction, and oxidative stress. Our previous study found elevated acrolein levels in hypoxic glioma cells and linked acrolein-induced DNA damage (Acr-dG) with poor GBM prognosis. However, the role of acrolein in GBM progression remains unclear. This study aims to elucidate the impact of acrolein on GBM. In vitro experiments demonstrated acrolein production under hypoxia, which increased glioma cell migration and spheroid formation. RNA sequencing identified five affected pathways: cell adhesion molecules, PI3K-AKT signaling, ECM-receptor interaction, MAPK signaling, and neuroactive ligand-receptor interaction. Acrolein downregulated NCAM (neural cell adhesion molecule) via the miR-30a-5p-AKT-GSK3β/β-catenin axis in GBM cell lines and patient-derived cells. Overexpressing NCAM reduced cell migration and spheroid formation. Lower NCAM levels in GBM tissues correlated with poor patient survival. This study suggests the potential of NCAM as a therapeutic target for GBM and provides insights into early detection and treatment strategies for this malignancy.

Loss of Brcc3 in Zebrafish Embryos Increases Their Susceptibility to DNA Damage Stress

DNA double-strand breaks (DSBs) represent one of the most severe forms of genetic damage in organisms, yet vertebrate models capable of monitoring DSBs in real-time remain scarce. BRCA1/BRCA2-containing complex subunit 3 (BRCC3), also known as BRCC36, functions within various multiprotein complexes to mediate diverse biological processes. However, the physiological role of BRCC3 in vertebrates, as well as the underlying mechanisms that govern its activity, are not well understood. To explore these questions, we generated brcc3-knockout zebrafish using CRISPR/Cas9 gene-editing technology. While brcc3 mutant zebrafish appear phenotypically normal and remain fertile, they exhibit significantly increased rates of mortality and deformity following exposure to DNA damage. Furthermore, embryos lacking Brcc3 display heightened p53 signaling, elevated γ-H2AX levels, and increased apoptosis in response to DNA-damaging agents such as ultraviolet (UV) light and Etoposide (ETO). Notably, genetic inactivation of p53 or pharmacological inhibition of Ataxia-telangiectasia mutated (ATM) activity rescues the hypersensitivity to UV and ETO observed in Brcc3-deficient embryos. These findings suggest that Brcc3 plays a critical role in DNA damage response (DDR), promoting cell survival during embryogenesis. Additionally, brcc3-null mutant zebrafish offer a promising vertebrate model for real-time monitoring of DSBs.

Exploring the mechanism of Suxin Hugan Fang in treating ulcerative colitis based on network pharmacology

As a traditional Chinese medicine formula used in clinical practice for an extended period, Suxin-Hugan-Fang (SXHGF) exhibits excellent anti-inflammatory properties. However, the efficacy of SXHGF in treating ulcerative colitis (UC) and its mechanism of action are still unclear. In this study, the therapeutic effects of SXHGF on UC were evaluated using network pharmacology and experimental validation, while also investigating its mechanism of action. By administering DSS to C57BL/6 mice to construct a mouse model of ulcerative colitis, the therapeutic effect of SXHGF on ulcerative colitis was evaluated based on weight loss percentage, disease activity index, colon length changes, and pathological conditions as indicators. The main chemical components of SXHGF were determined by LC-MS-QTOF method. The potential targets and mechanisms of action of SXHGF in the treatment of UC were inferred using bioinformatics methods, and further validated through ELISA, IHC, and Western blotting assays. The experimental results demonstrate that SXHGF can suppress oxidative stress and oxidative damage in the colon tissue of UC mice, and alleviate DSS-induced ulcerative colitis by inhibiting the JAK2/STAT3 and NFκB pathways.

Isolation of highly polar galloyl glucoside tautomers from Saxifraga tangutica through preparative chromatography and assessment of their in vitro antioxidant activity

In this work, the rapid and efficient preparation of isolated galloyl glucoside tautomer free radical inhibitors was investigated using Saxifraga tangutica as a raw material. Four highly polar galloyl glucoside tautomers, 3-O-galloyl-α-d-glucose ⇌ 3-O-galloyl-β-d-glucose (Fr2-1-1), 2-O-galloyl-α-d-glucose ⇌ 2-O-galloyl-β-d-glucose (Fr2-1-2/2-1-3), 1-O-galloyl-β-d-glucose (Fr2-2-1), and 6-O-galloyl-α-d-glucose ⇌ 6-O-galloyl-β-d-glucose (Fr2-3-1/Fr2-3-2), were obtained via two-step medium-pressure liquid chromatography (with solid loading instead of conventional liquid injection) and one-step high-performance chromatography coupled with on-line RPLC-DPPH techniques for targeted isolation. This separation integration technique not only increases sample intake and reduces time cost but also visualizes each step of targeted separation. All four compounds were isolated from the plant for the first time. In vitro antioxidant activity assays by DPPH (1,1‑diphenyl-2-picrylhydrazyl) revealed that Fr2-1-2/Fr2-1-3 (IC50: 5.52 ± 0.32 μM), Fr2-2-1 (IC50: 7.22 ± 0.57 μM), and Fr2-3–1/Fr2-3-2 (IC50: 7.36 ± 0.25 μM) had superior free radical scavenging abilities and that both were superior to that of quercetin (IC50: 18.61 ± 3.55 μM). Oxidative stress assays revealed that Fr2-1-2/Fr2-1-3 significantly inhibited oxidative stress damage in H2O2-induced HepG2 cells, decreased the level of ROS (P < 0.01) and protected hepatocytes. Combined with the current results, gallic acid showed greater antioxidant activity when H atoms were replaced at d-glucose –OH (C-2) than at the other three sites [–OH (C-1), –OH (C-6) and –OH (C-3)].

Capturing drought stress signals: The potential of dendrometers for monitoring tree water status.

The severity of droughts is expected to increase with climate change, leading to more frequent tree mortality and a decline in forest ecosystem services. Consequently, there is an urgent need for monitoring networks to provide early warnings of drought impacts on forests. Dendrometers capturing stem diameter variations may offer a simple and relatively low-cost opportunity. However, the links between stem shrinkage, a direct expression of tree water deficit (TWD), and hydraulic stress are not well understood thus far. In this study, we exposed two widespread conifers Pinus sylvestris and Larix decidua to lethal dehydration by withholding water and closely monitored TWD, midday water potential ($\psi $), and midday stomatal conductance ($g_{s}$) under controlled greenhouse conditions. We found strong relationships between the three variables throughout the dehydration process, particularly suggesting the potential for continuous $\psi $ predictions and stomatal closure assessments. However, the relationships decoupled during recovery from severe drought. We also identified TWD thresholds that signal the onset of drought stress and tissue damage, providing insights into stress impacts and recovery potential. While these findings are promising, challenges remain in practically transferring them to field set-ups by suitable TWD normalization. Importantly, we observed that midday $g_{s}$ was drastically reduced when TWD persisted overnight, providing a directly applicable drought stress signal that does not require normalization. In conclusion, while challenges remain, our results highlight the potential of dendrometers for monitoring tree water dynamics. Implementing dendrometer networks could support the development of early-warning metrics for drought impacts, enabling large-scale monitoring in diverse settings, such as urban areas and forest ecosystems.

Morphofunctional Features of Glomeruli and Nephrons After Exposure to Electrons at Different Doses: Oxidative Stress, Inflammation, Apoptosis

Kidney disease has emerged as a significant global health issue, projected to become the fifth-leading cause of years of life lost by 2040. The kidneys, being highly radiosensitive, are vulnerable to damage from various forms of radiation, including gamma (γ) and X-rays. However, the effects of electron radiation on renal tissues remain poorly understood. Given the localized energy deposition of electron beams, this study seeks to investigate the dose-dependent morphological and molecular changes in the kidneys following electron irradiation, aiming to address the gap in knowledge regarding its impact on renal structures. The primary aim of this study is to conduct a detailed morphological and molecular analysis of the kidneys following localized electron irradiation at different doses, to better understand the dose-dependent effects on renal tissue structure and function in an experimental model. Male Wistar rats (n = 75) were divided into five groups, including a control group and four experimental groups receiving 2, 4, 6, or 8 Gray (Gy) of localized electron irradiation to the kidneys. Biochemical markers of inflammation (interleukin-1 beta [IL-1β], interleukin-6 [IL-6], interleukin-10 [IL-10], tumor necrosis factor-alpha [TNF-α]) and oxidative stress (malondialdehyde [MDA], superoxide dismutase [SOD], glutathione [GSH]) were measured, and morphological changes were assessed using histological and immunohistochemical techniques (TUNEL assay, caspase-3). The study revealed a significant dose-dependent increase in oxidative stress, inflammation, and renal tissue damage. Higher doses of irradiation resulted in increased apoptosis, early stages of fibrosis (at high doses), and morphological changes in renal tissue. This study highlights the dose-dependent effects of electrons on renal structures, emphasizing the need for careful consideration of the dosage in clinical use to minimize adverse effects on renal function.

The Effects of Antioxidant Supplementation on Soccer Performance and Recovery: A Critical Review of the Available Evidence

Background Soccer is linked to an acute inflammatory response and the release of reactive oxygen species (ROS). Antioxidant supplements have shown promising effects in reducing muscle damage and oxidative stress and enhancing the recovery process after eccentric exercise. This critical review highlights the influence of antioxidant supplements on performance and recovery following soccer-related activity, training, or competition. Methods: English-language publications from the main databases that examine how antioxidant-based nutrition and supplements affect the recovery process before, during, and after soccer practice or competition were used. Results: Coenzyme Q10 (CoQ10), astaxanthin (Asx), red orange juice (ROJS), L-carnitine (LC), N-acetyl cysteine (NAC), beetroot (BET), turmeric root, and tangeretin reduce muscle damage (creatine kinase, myoglobin, cortisol, lactate dehudrogenase, muscle soreness). Tangeretin, docosahexaenoic acid (DHA), turmeric root, and aronia melanocarpa restrict inflammation (leukocytes, prostalagdin E2, C-reactive protein, IL-6 and 10). Q10, DHA, Asx, tangeretin, lippia citriodora, quercetin, allopurinol, turmeric root, ROJS, aronia melanocarpa, vitamins C-E, green tea (GTE), and sour tea (STE) reduce oxidative stress (malondialdehude, glutathione, total antioxidant capacity, superoxide dismutases, protein carbonyls, ascorbate, glutathione peroxidase, and paraoxonase 1). BET and NAC reinforce performance (endurance, jump, speed, strength). Conclusions: Further research is needed to determine the main mechanism and the acute and long-term impacts of antioxidant supplements in soccer.

Enhancement of Tomato Fruit Quality Through Moderate Water Deficit

In arid areas, water shortage has become a major bottleneck limiting the sustainable development of agriculture, necessitating improved water use efficiency and the full development of innovative water-saving irrigation management technologies to improve quality. In the present study, tomato (Solanum lycopersicum cv. Micro Tom) fruits were used as materials, and different irrigation frequencies were set during the fruit expansion stage. The normal treatment (CK) was irrigated every three days, while the water deficit treatments were irrigated at varying frequencies: once every 4 days (T1), 5 days (T2), 6 days (T3), 7 days (T4), and 8 days (T5). These corresponded to 80%, 70%, 60%, 50%, and 40% of the maximum field moisture capacity (FMC), respectively, with CK maintaining full irrigation at 90% of the maximum FMC. The water deficit treatment T3, with less stress damage to plants and the most significant effect on fruit quality improvement, was selected based on plant growth indices, photosynthetic characteristics, chlorophyll fluorescence parameters, and fruit quality indices, and its effects on carotenoids, glycolic acid fractions, and volatile compounds during tomato fruit ripening were further investigated. The outcome indicated that moderate water deficit significantly increased the carotenoid components of the tomato fruits, and their lycopene, lutein, α-carotene, and β-carotene contents increased by 11.85%, 12.28%, 20.87%, and 63.89%, respectively, compared with the control fruits at the ripening stage. The contents of glucose and fructose increased with the development and ripening of the tomato fruits, and reached their maximum at the ripening stage. Compared to the control treatment, the moderate water deficit treatment significantly increased the glucose and fructose levels during ripening by 86.70% and 19.83%, respectively. Compared to the control conditions, water deficit conditions reduced the sucrose content in the tomato fruits by 27.14%, 18.03%, and 18.42% at the mature green, turning, and ripening stages, respectively. The moderate water deficit treatment significantly increased the contents of tartaric acid, malic acid, shikimic acid, alpha ketoglutaric acid, succinic acid, and ascorbic acid, and decreased the contents of oxalic acid and citric acid compared to the control. The contents of total soluble sugar and total organic acid and the sugar–acid ratio were significantly increased by 48.69%, 3.71%, and 43.09%, respectively, compared with the control at the ripening stage. The moderate water deficit treatment increased the fruit response values to each sensor of the electronic nose, especially W5S, which was increased by 28.40% compared to the control at the ripening stage. In conclusion, during the ripening process of tomato fruit, its nutritional quality and flavor quality contents can be significantly improved under moderate (MD) deficit irrigation treatment. The results of this experiment can lay the foundation for the research on the mechanism of water deficit aiming to promote the quality of tomato fruit, and, at the same time, provide a theoretical basis and reference for tomato water conservation and high-quality cultivation.

Protective Effect of Biochanin A on Gamma Radiation-Induced Oxidative Stress, Antioxidant Status, Apoptotic, and DNA Repairing Molecules in Swiss Albino Mice.

Radiation therapy is indispensable in medical practice but often causes adverse effects on healthy tissues, necessitating the search for natural radioprotectors. This study investigates the protective effect of Biochanin A (BCA) against gamma radiation-induced oxidative stress and DNA damage in Swiss albino mice. Gamma radiation, a potent ionizing source, generates reactive oxygen species (ROS) that damage cellular biomolecules, including DNA. Antioxidants play a crucial role in neutralizing ROS and preventing oxidative damage. Swiss albino mice were divided into control, BCA control (10 mg/kg body weight), radiation alone (7 Gy), and radiation+ BCA pretreatment groups. BCA, a natural isoflavone with known antioxidant and cytoprotective properties, was administered intraperitoneally before radiation exposure. After irradiation, lipid peroxidation levels, antioxidant enzyme activities/level (superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione), expression levels of DNA repair genes (P53, P21, GADD45α), apoptotic markers (Bax, Bcl-2, Caspase-3, -9 and Cytochrome-C), and inflammatory marker (NF-κB) were analyzed in small intestine tissue. Our findings indicate that gamma radiation significantly elevated lipid peroxidation levels and altered antioxidant enzyme activities, indicating oxidative stress. However, BCA pretreatment mitigated these effects by bolstering antioxidant defences, reducing radiation-induced oxidative damage. Additionally, BCA altered apoptotic markers, NF-κB expression, promoting cell survival mechanisms. At the molecular level, BCA pretreatment upregulated key DNA repair genes (P53, P21, GADD45α), crucial for repairing radiation-induced DNA damage and maintaining genomic stability. These results underscore BCA potential as a radioprotector, suggesting its efficacy in mitigating radiation-induced oxidative stress and preserving cellular integrity. In conclusion, BCA demonstrates promising radioprotective properties by attenuating oxidative stress, enhancing antioxidant defences, modulating apoptotic pathways, and promoting DNA repair mechanisms following gamma radiation exposure. Further research is necessary to elucidate its precise mechanisms of action and explore its potential therapeutic applications in radiation oncology and environmental radioprotection.

Efficacy of Omega-5 NanoPSO Treatment in the Hippocampus, Through Antioxidant Mechanisms, After an Ischemia/Reperfusion Injury, in Murine Model

Stroke is the third cause of death worldwide and a health problem, and current therapy continues to be very poor. It promotes an alteration associated with excitotoxicity, oxidative stress, and inflammatory processes, exacerbating the damage in the brain. Although cortical areas are the most affected by stroke, the hippocampus can be impacted in the long term through the pathways it connects with these areas, which are associated further with motor alterations; this encourages the search for new therapeutic approaches. Omega-5, being an antioxidant, participates in regulating oxidative stress. A recently designed nanoemulsified compound coupled with pomegranate seed oil (NanoPSO) maintains bioavailability in the body for longer. Omega-5 NanoPSO is more effective in different models of neurodegenerative diseases and metabolic disorders. Therefore, it is important to analyze the effect of omega-5 NanoPSO on ischemic damage through changes in the hippocampus, oxidative mechanisms, and behavioral outcomes. Male Wistar rats were used in five groups; three groups were subjected to an ischemic event through bilateral occlusion of the carotid arteries. An ischemia group received omega-5 NanoPSO after injury, and another group received omega-5 NanoPSO performed two weeks before the ischemic event and three weeks after the surgical process. The control and sham groups did not show changes in the hippocampus and behavior. In the ischemia group, neuronal loss, oxidative stress, and a higher expression of astrocytes were maintained in the hippocampal region, and behavior was modified. In the post and pre-treatment group with omega-5 NanoPSO, we observed reduced damage, glial proliferation, and oxidative stress. It increased neuron survival in the hippocampal region and improved the locomotion. These results highlight its promise for use in clinical settings to treat patients suffering from ischemic brain injury.

Activation of lysosomal Ca2+ channels mitigates mitochondrial damage and oxidative stress.

Elevated levels of plasma-free fatty acids and oxidative stress have been identified as putative primary pathogenic factors in endothelial dysfunction etiology, though their roles are unclear. In human endothelial cells, we found that saturated fatty acids (SFAs)-including the plasma-predominant palmitic acid (PA)-cause mitochondrial fragmentation and elevation of intracellular reactive oxygen species (ROS) levels. TRPML1 is a lysosomal ROS-sensitive Ca2+ channel that regulates lysosomal trafficking and biogenesis. Small-molecule agonists of TRPML1 prevented PA-induced mitochondrial damage and ROS elevation through activation of transcriptional factor EB (TFEB), which boosts lysosome biogenesis and mitophagy. Whereas genetically silencing TRPML1 abolished the protective effects of TRPML1 agonism, TRPML1 overexpression conferred a full resistance to PA-induced oxidative damage. Pharmacologically activating the TRPML1-TFEB pathway was sufficient to restore mitochondrial and redox homeostasis in SFA-damaged endothelial cells. The present results suggest that lysosome activation represents a viable strategy for alleviating oxidative damage, a common pathogenic mechanism of metabolic and age-related diseases.

Flavonoids Mitigate Nanoplastic Stress in Ginkgo biloba.

Microplastics/nanoplastics are a top global environmental concern and have stimulated surging research into plant-nanoplastic interactions. Previous studies have examined the responses of plants to nanoplastic stress at various levels. Plant-specialized (secondary) metabolites play crucial roles in plant responses to environmental stress, whereas their roles in response to nanoplastic stress remain unknown. Here, we systematically examined the physiological and biochemical responses of Ginkgo biloba, a species with robust metabolite-driven defenses, to polystyrene nanoplastics (PSNPs). PSNPs negatively affected seedling growth and induced phytotoxicity, oxidative stress, and nuclear damage. Notably, PSNPs caused significant flavonoid accumulation, which enhances plant tolerance and detoxification against PSNP stress. To determine whether this finding is universal in plants, we subjected Arabidopsis, poplar, and tomato to PSNP stress and verified the common response of enhanced flavonoids across these species. To further confirm the role of flavonoids, we employed genetic transformation and staining techniques, validating the importance of flavonoids in mitigating excessive oxidative stress induced by NPs. Matrix analysis of transgenic plants with enhanced flavonoids further demonstrated altered downstream pathways, allocating more energy towards resilience against nanoplastic stress. Collectively, our results reveal the flavonoid multifaceted roles in enhancing plant resilience to nanoplastic stress, providing new knowledge about plant responses to nanoplastic contamination.